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Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events

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Abstract

The advent of immune checkpoint inhibitors (ICIs) has led to noteworthy progressions in the management of diverse cancer types, as evidenced by the pioneering “ipilimumab” medication authorized by US FDA in 2011. Importantly, ICIs agents have demonstrated encouraging potential in bringing about transformation across diverse forms of cancer by selectively targeting the immune checkpoint pathways that are exploited by cancerous cells for dodging the immune system, culminating in progressive and favorable health outcomes for patients. The primary mechanism of action (MOA) of ICIs involves blocking inhibitory immune checkpoints. There are three approved categories including Programmed Death (PD-1) inhibitors (cemiplimab, nivolumab, and pembrolizumab), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (Ipilimumab), and Programmed Death-Ligand 1 (PDL-1) (Avelumab). Although ICIs promisingly increase therapeutic response and cancer survival rates, using ICIs has demonstrated some limitations including autoimmune reactions and toxicities, requiring close monitoring. The present review endeavors to explicate the underlying principles of the MOA and pharmacokinetics of the approved ICIs in the realm of cancer induction, including an appraisal of their level of practice-based evidence.

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Abbreviations

CDC:

Center for Disease Control and Prevention

ICIs:

Immune checkpoint inhibitors

CDC:

Center for disease control and prevention

PD-1:

Programmed death

PDL-1:

Programmed death-ligand 1

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

irAE:

Immune-related adverse events

NK:

Natural killer

NSCLC:

Non-small cell lung cancer

HHis:

Hedgehog inhibitors

NSC:

Neural stem cells

HNSCC:

Head and neck squamous cell carcinoma

CSCC:

Cutaneous squamous cell carcinoma

EGFR:

Epidermal growth factor receptor

NIR-PIT:

Near-infrared photoimmunotherapy

ALK:

Anaplastic lymphoma kinase

TMB:

Tumor mutational burden

MOA:

Mechanism of action

uHCC:

Unresectable hepatocellular carcinoma

ITIM:

Immunoreceptor tyrosine-based inhibitory motif

ITSM:

Immunoreceptor-based switch motif

NSC:

Neural stem cells

NMIBC:

Non-muscle-invasive bladder cancer

RCT:

Randomized controlled trial

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Authors and Affiliations

  1. Department of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran

    Seyed Mohammadmahdi Meybodi

  2. Department of Chemistry, Iran University of Science and Technology, Tehran, 1684613114, Iran

    Bahareh Farasati Far

  3. Babol Noshirvani University of Technology, Shariati Ave, Babol, Mazandaran, Iran

    Ali Pourmolaei

  4. Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, University of Pécs, Pécs, Hungary

    Farid Baradarbarjastehbaf

  5. Department of Pharmacology, Faculty of Pharmacy, Eastern Mediterranean University, 99628, Famagusta, Turkey

    Maryam Safaei

  6. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Niloufar Mohammadkhani

  7. Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran

    Ali Akbar Samadani

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BFF, MS, and SMM wrote the paper. FB, AP, AAS, and NM, provided writing assistance and reviewing the final version of the manuscript.

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Meybodi, S.M., Farasati Far, B., Pourmolaei, A. et al. Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events. Med Oncol 40, 243 (2023). https://doi.org/10.1007/s12032-023-02114-6

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